Porcine epidemic diarrhea (PED) is highly contagious and is characterized by dehydration, diarrhea, and high mortality in swine, particularly young piglets. The causative agent, porcine epidemic diarrhea virus (PEDV), is a single stranded, positive sense RNA virus identified to the Alphacoronoavirus genus of the family Coronaviridae. PEDV has a total genome size of approximately 28 kb and contains 7 open reading frames. Symptoms of PEDV infection are often similar to those caused by transmissible gastroenteritis virus (TGEV), also a member of the Coronaviridae. It should be noted that cross protection between PEDV and TGEV is not generally observed, the overall viral nucleotide sequences being at most about 60% similar.
PED was likely first observed in Europe circa 1970, and the causative virus was subsequently characterized (see for example M. Pensaert et al. Arch. Virol, v. 58, pp 243-247, 1978 and D. Chasey et al., Res. Vet Sci, v. 25, pp 255-256, 1978). PED disease was generally considered unknown in North America until 2013, at which point widespread outbreaks commenced, and severe economic losses to the swine industry resulted. Prototype North American isolates have remained genetically closely related (i.e. with overall nucleotide identity generally over 99%), and are similar to Asian strains characterized there within a few years prior to the North American outbreaks. PEDV generally grows poorly in culture, and there is a need to identify both particular strains and culture conditions that are appropriate for the culturing of sufficient virus for commercial vaccine preparation. Additionally, there is a need to develop vaccines that provide effective cross protection against known isolates of PEDV, and which are expected to provide effective cross protection against evolving, non-prototype PEDV strains.
Additionally, variant strains of PEDV (for example Calaf14, see SEQ ID NOS 1, 4 for S protein sequence) have been recently identified in Europe, which are recognizably different from known European strains. Such variant strains (similar to Calaf14 based on spike protein sequence) have also appeared in North America, and previously in Asia, and may be more similar to each other than to prototype strains. Accordingly, there is a need to identity both vaccine strains and appropriate vaccine compositions that will be effective against current and emerging worldwide outbreaks of PEDV, thus providing needed cross protection.
Porcine deltacoronavirus (PDCoV) is a member of a novel group of coronaviruses which were initially identified as “Group 3c coronaviruses” by Woo et al. (J Virol., 83(2):908-917, 2009) in various avian species. Subsequently, these viruses were reclassified as “deltacoronaviruses”, and have been identified in other avian species, as well as in pigs (Woo et al., J Virol., 86(7):3995-4007, 2012; Marthaler et al., Genome Announc., 2(2):e00278-14, 2014; Li et al., Genome Announc., 2(2):e00278-14, 2014; Wang et al., Genome Announc., 2(2):e00291-14, 2014; Wang et al., Emerg. Infect. Dis., 20(7):1227-1230, 2014). The genome size of deltacoronaviruses (˜25-26 kb) is smaller in size than PEDV and other alphacoronaviruses, which can approach 32 kb.
PDCoV has to date been detected at least in Hong Kong, Canada, China and the US, and while the death rate in piglets reported for PDCoV infections (30-40%) is apparently lower than that typically observed with PEDV infection, interpretation of field data is often difficult since co-infections with PEDV and other intestinal pathogens are common (EFSA Journal, 12(10):3877, 2014). While more knowledge on the pathogenesis and clinical implications of PDCoV is needed, this recently-identified virus appears to be an emerging pathogen in pigs. Thus, efficacious vaccine compositions for treating and preventing disease caused by PDCoV are desired, as are combination vaccines that prevent and/or treat both PEDV and PDCoV diseases.